Abstract
BackgroundOur previous work found that mouse embryos could invade malignant cancer cells. In the process of implantation, embryo trophoblast cells express matrix metalloproteinases and the invasive ability of trophoblast cells is proportional to matrix metalloproteinase-9 protein expression. So the purpose of this study is to observe the effects of mouse embryos on human ovarian cancer cells in the co-culture environment in vitro and explore the possible mechanism of matrix metalloproteinase-9.MethodsSeveral groups of human ovarian cancer cells HO8910PM were co-cultured with mouse embryos for different time duration, after which the effects of mouse embryos on morphology and growth behavior of HO8910PM were observed under the light microscope real-time or by H.E staining. Apoptosis was detected under laser confocal microscope by Annexin V-EGFP/PI staining in situ. Invasion ability of tumor cells was studied by transwell experiments. After matrix metalloproteinase 9 (MMP −9) activity was inhibited by MMP-9 Inhibitor I, the interaction between mouse embryos and human ovarian cancer cells HO8910PM was observed.ResultsMouse embryos were able to invade co-cultured human ovarian cancer cell layer which extended in the bottom of the culture dish, and gradually pushed away tumor cells to form their own growth space. The number of apoptosis tumor cells surrounding the embryo increased under laser confocal microscope. After co-cultured with mouse embryos, tumor cells invasive ability was lowered compared with the control group. After MMP-9 activity was inhibited, the interaction between mouse embryos and HO8910PM cells had no significant difference compared with the normal MMP-9 activity group.ConclusionMouse embryos were able to invade human ovarian cancer cells in vitro and form their own growth space, promote apoptosis of human ovarian cancer cells and lower their invasive ability. The mouse embryo was still able to invade human ovarian cancer cells after MMP-9 activity was inhibited.
Highlights
Ovarian cancer is one of the most common female genital cancers and its incidence rate ranks only second to cervical cancer and uterine cancer while its fatality rate is in the first place among various types of gynecologic cancers [1]
In our previous research we found that mouse embryos widely invaded malignant cells which seemingly implied that early embryos had more invasive ability than malignant cells [7]
Four-to sixweek-old female mice were superovulated by an i.p. injection of 7.5 IU Pregnant Mare Serum Gonadotrophin (PMSG)(Everest Biotech Ltd., Oxfordshire, UK) per mouse followed by a second i.p. injection of 7.5 IU Human Chorionic Gonadotropin(HCG) (Everest Biotech Ltd., Oxfordshire, UK) 48 h later
Summary
Ovarian cancer is one of the most common female genital cancers and its incidence rate ranks only second to cervical cancer and uterine cancer while its fatality rate is in the first place among various types of gynecologic cancers [1]. The similarity of early embryos and malignant cells attracts the attention of scientists. Murray and his colleagues demonstrated that early embryos and malignant cells shared significant similarity on proliferation, division, invasion, immune escape and angiogenesis, etc [6]. In our previous research we found that mouse embryos widely invaded malignant cells which seemingly implied that early embryos had more invasive ability than malignant cells [7]. Our previous work found that mouse embryos could invade malignant cancer cells. The purpose of this study is to observe the effects of mouse embryos on human ovarian cancer cells in the co-culture environment in vitro and explore the possible mechanism of matrix metalloproteinase-9
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